The present invention relates to a method for preventing and/or alleviating a psychiatric disorder, and/or effectuating sedation, comprising administering a benzylisoquinoline or bisbenzylisoquinoline derivative derived from lien tzehsin, and health food containing said derivative.
Psychiatric disorders are steadily increasing, reflecting the recent stressful society. The psychiatric disorders raise a serious social problem as the patients are inadaptable with society, and also an important issue from the viewpoint of medical economy. Drugs that are capable of affecting mental activity and behavior as the principal pharmacological action are called psychotropic drug, which are classified into integration ataxia drugs, mood-stabilizing drugs, antidepressants, antianxiety drugs, hypnotics, sedative drugs, antipsychotic drugs, antiepileptic drugs, alcohol deterrents, antiparkinson drugs, antidementia drugs, and the like. Various drugs with different action mechanisms have been developed and used for treatment of various psychiatric disorders.
For example, anxiety disorders, which are becoming more popular and an important social problem particularly recently, are generally classified into phobic anxiety disorder, agoraphobia, sociophobia, panic disorder, generalized anxiety disorder, obsessive compulsive disorder, certain phobia, and other anxiety disorders. These symptoms often appear in a complicated way.
The symptoms of depression include depressive condition, anhedonia, psychomotor retardation, thinking/cognitive dissonance, anxiety and impatience, autonomic nerve symptom, and the like.
Integration ataxia is a disease wherein integrating ability, an ability to integrate thinking, behavior, and emotion to fit for purpose, deteriorates gradually over an extended period of time and certain hallucination, delusion, and extremely unorganized behavior are observed during the deterioration process, but is rather indistinguishable from depression, maladjustment, or the like, and thus the final diagnosis thereof is made by the symptoms such as hallucination, delusion, and the like. However, the causes of the sickness are yet to be clearly understood, and the claim that integration ataxia is a single disease is still under a cloud.
Examples of the therapeutic drugs for the symptoms above are antidepressants currently used including tricyclic antidepressants such as imipramine, clomipramine, and trimipramine; tetracyclic antidepressants such as maprotiline and mianserin; triazolopyridine-based trazodone; benzketoxime-based selective serotonin reuptake inhibitor (SSRI) fluvoxamine; and the like.
Examples of the sleeping drugs include barbituric hypnotics used for quite a long time; benzodiazepine-based hypnotics such as triazolam, etizolam, brotizolamo, flunitrazepam, nitrazepam, quazepam, zopiclone and zolpidem which have been developed more recently; and the like. Further, favorable examples of the antianxiety drugs include the benzodiazepine-based drugs above, fluvoxamine and paroxetine, which are called SSRIs, and the like.
Drugs that have an action on the intracerebral dopamine nervous system have been used for treatment of integration ataxic, but also raised problems of extrapyramidal tract disorders (parkinsonian syndromes) as the adverse reactions, i.e., the adverse reactions observed as catalepsy in animal experiment systems. More recently, atypical antipsychotic drugs, which have an action also on the serotonin nervous system, were introduced and proven to be more effective in treating the disease. Other therapeutic drugs which have been used for treatment are called minor tranquilizers, which act on the cerebral limbic system in the brain such as thalamus, hippocampus, amygdala nidus, and the like and are said to alleviate selectively emotional disorders such as anxiety and stress and stabilize autonomic activities. Typical therapeutic drugs thereof are benzodiazepine compounds and azapyrone-based compounds. However, these drugs also carry the problem of side reactions such as motor coordination disorder, induction of catalepsy, and convulsive action induced by strychnine or picrotoxin.
However, it is pointed out that tricyclic or similar cyclic antidepressants cause anticholinergic actions such as dry mouth, eye adjustment disorder (misty vision), constipation, and dysuria, increase in body weight presumably caused by the antihistamic action, adrenolytic actions such as hypotension, dizziness, and stagger, adverse reactions such as cardiotoxic diseases, as well as acute poisoning by excessive intake.
It is also pointed out that the SSRI-group drugs may cause serotonin syndromes, although the adverse reactions thereof are significantly suppressed.
On the other hand, Saint John's Wort, for example, is famous as a health food for alleviating the various symptoms caused by the abnormality in the central nervous system, and said to be useful in the treatment of depression (Linde et al., British Medical Journal, 313 (1996) 253). Saint John's Wort, also called rose of Sharon, has long been used as a therapeutic drug for treatment of wound and neuralgia. Recently, it is widely used in the form of health food tablet mainly in Europe and North America as well as in Japan.
However, a component contained in Saint John's Wort is known to have a serious adverse reaction, photohypersensitivity, and another component a side reaction affecting the kinetics of cyclosporine metabolism in the body.
Lotus (Nelumbo nucifera Gaertner), a plant in water-lily family, has been widely used from root to flower as the ingredients for herbal cuisines from ancient days. In particular, lien tzehsin, green embryo of mature seed (Nelumbinis embryo), has been used in the oriental medicine for treatment of febrile diseases, care-laden vomiting of blood, and oneirogmus as it is said to have functions to reduce fevers, stop bleeding, slow ejaculation, and others (“Encyclopedia of Japanese and Chinese Medicines”, Tsuneo Namba, p. 216 and “Comprehensive Dictionary of Chinese Medicines”, Ed., Shanghai Science and Technology Publication and Shogakkan, (1985) p. 2750).
In studies on the active components mainly centered on the alkaloids of lien tzehsin, data on structural determination of the benzylisoquinoline and bisbenzylisoquinoline alkaloids were reported (Furukawa et al., Yakugaku Zasshi, 84 (1965) p. 335, Tomita et al., Chemical Pharmaceutical Bulletin, 13 (1965) p. 39 and Kunitomo et al., Phytochemistry, 12 (1973) p. 669), but no pharmacological effects of the alkaloids were reported except a kind of bisbenzylisoquinoline alkaloid, neferine.
On the other hand, with respect to recent studies on pharmacological effects of lien tzehsin, Nishibe et al. found the defervescent, antihypertensive, and antipsychotic actions thereof short time ago, but did not show any detailed grounds for the actions (Nishibe et al., Journal of Natural Products, 49 (1986) p. 547). Specifically, Nishibe et al. only disclosed (1) purification and isolation of four alkaloids from lien tzehsin, (2) animal tests concerning the antihypertensive activity, and (3) that one of the four alkaloids, neferine, exhibited an antihypertensive action, but there were no grounds for the defervescence and antipsychotic actions and no specific data concerning the antihypertensive activity (Nishibe et al., Journal of Natural Products, 49 (1986) p. 547).
In addition, the following two studies were reported at the meeting of the Pharmaceutical Society of Japan in 2002. Sato et al. reported from their rat studies that lien tzehsin had a thermoregulating function (Sato et al., Abstract of the 123rd annual meeting of the Pharmaceutical Society of Japan, No. 2, p. 112), while Kawashima et al. an anti-osteoporosis action of a lien tzehsin extract in the human osteoblast system (Kawashima et al., Abstract of the 123rd annual meeting of the Pharmaceutical Society of Japan No. 2, p. 146).
On the other hand, the inventors reported from mice studies that a component of lien tzehsin, neferine, exhibited a locomotor activity-inhibiting action (Ito et al., Abstract of the 50th annual meeting of the Japanese Society of Pharmocognosy, p. 116).
However, there are no known reports about the pharmacological effects of lien tzehsin components other than those described above.
An object of the present invention is to provide a method and a health food for preventing and/or alleviating a psychiatric disorder, and/or for effectuating sedation, in particular a method and a health food for preventing and/or alleviating at least one symptom selected from the group consisting of integration ataxia, depression, anxiety disorder, dysthymia, manic state, epilepsy, and sleep disorder, in which a natural product-derived substance safer even when taken for an extended period of term is used.